Hormone replacement therapy (HRT) provides relief of menopausal symptoms, reverses atrophic urogenital changes, prevents osteoporosis, and produces favorable lipoprotein effects. Continuous combined HRT using 2.5 mg of medroxyprogesterone was designed to increase patient compliance by eliminating withdrawal bleeding while at the same time retaining the beneficial effects of HRT. There are limited long-term data, however, regarding the safety of continuous combined HRT. Of concern are reports of endometrial carcinoma arising in women receiving continuous HRT with low-dose progestin. Eight cases of women who developed endometrial carcinoma while on this regimen are presented. The possible increased risk of endometrial cancer associated with this regimen may be related to inadequate progestin dose, prior use of unopposed estrogen, poor patient compliance, use of less effective progestins, less efficient reversal of hyperplasia, and the use of progestin continuously.